Biomedicine Weekly · Week 41, 2026 · 10.05 — 10.11
CBA FRONTIER INSIGHTS
This issue's figures
Open a card for the chart; click again to closeNobel Honors Optogenetics and Chirality; Retatrutide Redefines Obesity Weight Loss
This week the 2026 Nobel Prizes recognized optogenetics in Medicine and asymmetric amplification in Chemistry, while David Liu detailed how base and prime editing have reached the clinic. Retatrutide became the first triple agonist to publish Phase III efficacy in NEJM and The Lancet, with nearly a quarter of participants with obesity losing over 35% of body weight, as Chinese GLP-1 rivals posted 52-week weight losses above 19%. Two B7-H3 ADCs each hit an overall survival hazard ratio of 0.46 in relapsed small cell lung cancer, and the FDA approved atezolizumab for Stage III mismatch repair deficient colon cancer plus four other approvals. On the research front, whole-embryo lineage tracing and the complete adult male fly connectome landed in Science and Cell.
Nobel Laurels and Genome Editors in Clinic
On this pageThe 2026 Medicine Nobel went to Karl Deisseroth, Peter Hegemann and Georg Nagel for optogenetics, building on channelrhodopsin from Chlamydomonas to make rat neurons light-responsive. Chemistry honored Henri Kagan and Kenso Soai, sharing 12 million Swedish kronor, for amplification of handedness asymmetries that underpin synthesis of drugs, materials and perfumes. David Liu described base and prime editing advancing clinically: at least 23 trials, a 2022 triple-base-edited CAR-T achieving complete remission in a T cell leukemia patient, and a bespoke prime editing therapy for KJ Mulun's urea cycle disorder.
Medicine Nobel awarded for brain ‘switch’ that controls neurons with light
Karl Deisseroth of Stanford University, Peter Hegemann of Humboldt University of Berlin and Georg Nagel of the University of Würzburg have won the 2026 Nobel Prize in Physiology or Medicine for their discoveries in optogenetics. Working at the Max Planck Institute of Biochemistry in the early 2000s, Hegemann and Nagel discovered channelrhodopsin, a light-sensitive protein from the alga Chlamydomonas reinhardtii; Deisseroth and colleagues then showed the gene could make rat neurons fire in response to light. The technique lets researchers control individual neurons and brain circuits to study effects on behaviour.
Chemistry Nobel awarded for solving mystery of how ‘handed’ organic molecules can emerge
The Royal Swedish Academy of Sciences in Stockholm awarded the 2026 Nobel Prize in Chemistry to Henri Kagan of University of Paris-Sud and Kenso Soai of Tokyo University, announced on 7 October. The two share the 12-million Swedish kronor (US$1.2-million) prize for showing how living organisms can produce just one of two mirror-image forms of molecules: Kagan demonstrated amplification of tiny handedness asymmetries in the 1980s, and Soai showed in the 1990s that a one-handed molecule can catalyse more products of its own chirality. The work underpins how chemists design reactions to make drugs, materials and perfumes.
youtube.com10.05David Liu: Base Editing and Prime Editing Move from Engineered Proteins to the Clinic
David Liu described base editing and prime editing as engineered proteins that modify DNA at specified sites without double-strand breaks or donor templates. At least 23 clinical trials were using the editors by the time of the talk, with first in vivo base editing results reported at the end of 2023 and the FDA recently clearing the first prime editing trial. Cases include a 2022 CAR-T therapy carrying three base edits that produced complete remission in a T cell leukemia patient, and a bespoke prime editing therapy for KJ Mulun's urea cycle disorder caused by a premature stop codon.
Obesity and Diabetes Drugs Raise the Bar
On this pageRetatrutide, the first GIP/GLP-1/glucagon triple agonist to complete Phase III, published in NEJM and The Lancet the same day; nearly a quarter of participants with obesity lost over 35% of body weight. In TRIUMPH, 1,152 people with type 2 diabetes and obesity lost up to 20.8% over 80 weeks, though 9 mg showed higher discontinuation (11.6%) than 12 mg (7.7%); Lilly plans to file in early 2027. Zhongsheng's RAY1225 cut weight 22.24% at 52 weeks, beating Borui's BGM0504 at 19.2%. Hengrui's oral HRS-7535 beat dapagliflozin on HbA1c in OUTSTAND-2, with falls of 1.50-1.68%.
Retatrutide Phase III Results Appear in NEJM and The Lancet as Nearly a Quarter With Obesity Lose Over 35% of Body Weight
Retatrutide, the first triple hormone receptor agonist to complete Phase III with key efficacy data, was published in NEJM and The Lancet on the same day. The Eli Lilly drug activates GIP, GLP-1 and glucagon receptors in a single molecule and is given as a once-weekly subcutaneous injection. Nearly a quarter of participants with obesity lost more than 35% of their body weight.
RAY1225 Cuts Weight 22.24% at 52 Weeks in Phase III, Beating BGM0504's 19.2%
RAY1225 injection, from Zhongsheng Pharmaceutical, met the primary endpoint in its Phase III weight-loss trial, with the 9 mg group losing 22.24% of baseline body weight over 52 weeks. Days earlier at EASD 2026, Borui Pharmaceutical's BGM0504 reported full Phase III data, with its 15 mg group losing 19.2% over 52 weeks. The two domestic GLP-1 candidates now post headline results exceeding the levels shown here for established comparators.
NEW RETATRUTIDE DATA: 12 mg barely beat 9 mg, and more people quit on 9 mg than 12 mg. What's going on?
In the TRIUMPH phase 3 trial of retatrutide, a GIP/GLP-1/glucagon triple agonist, 1,152 people with type 2 diabetes and obesity lost 12.7%, 19.1%, and 20.8% of body weight over 80 weeks on 4, 9, and 12 mg respectively, versus 4.0% on placebo. Discontinuation for adverse events was higher on 9 mg (11.6%) than on 12 mg (7.7%), and community discussion of the data questions whether the top dose is worth it. Lilly plans to file for approval in early 2027.
Hengrui Oral GLP-1 Agonist HRS-7535 Beats Dapagliflozin on HbA1c in Phase 3 OUTSTAND-2
HRS-7535, Hengrui Pharma's oral small-molecule GLP-1 receptor agonist, met non-inferiority versus dapagliflozin in the China phase 3 OUTSTAND-2 trial in type 2 diabetes patients inadequately controlled on metformin. HbA1c fell 1.50% to 1.68% across the 30 mg, 60 mg and 90 mg doses, versus 1.28% with dapagliflozin; the 90 mg dose was superior. Full methods are set for publication in Nature Medicine.
Deal-Making and Phase III Oncology Wins
On this pageNovartis paid $575 million upfront, up to $7.2 billion in milestones, for global rights to Abogen's mRNA CD19 T cell engager ABO2203, already published in Cell for refractory immune thrombocytopenia. Two B7-H3 ADCs, YL-201 and HS-20093, each hit an overall survival hazard ratio of 0.46 in relapsed small cell lung cancer Phase III trials. Epkinly plus R-CHOP cut progression or death risk by 51% in first-line DLBCL, beating Polivy and Monjuvi benchmarks. Iberdomide combination therapy reached 42 months median PFS in relapsed myeloma (HR 0.49), and Takeda's TAK-279 proved superior to deucravacitinib in psoriasis, with over 2.5-fold more complete clearance at week 16.
Novartis Pays $575 Million Upfront for Global Rights to Abogen mRNA T Cell Engager ABO2203
Novartis has licensed global rights to ABO2203, an mRNA-encoded CD19-targeted T cell engager, from Abogen Biosciences, with an option on follow-on RNA projects. The deal includes $575 million upfront and up to $7.2 billion in milestones, for a total of $7.775 billion. Two weeks before the announcement, a Ruijin Hospital team and Abogen published an exploratory clinical study of the molecule in refractory immune thrombocytopenia in Cell.
Two B7-H3 ADCs Post Phase III OS Wins With Hazard Ratio 0.46 in Relapsed Small Cell Lung Cancer
Two B7-H3 antibody-drug conjugates delivered Phase III overall survival wins in relapsed small cell lung cancer at the September 2026 WCLC presidential forum in Seoul. Tambotatug pelitecan (YL-201, from MediLink Therapeutics) in TAISHAN-302 and risvutatug rezetecan (HS-20093, from Hansoh/GSK) in ARTEMIS-008 each hit an overall survival hazard ratio of 0.46, rewriting a second-line standard that had held for three decades and putting B7-H3 ADCs in direct contention with DLL3 bispecifics in the same setting.
AbbVie, Genmab's Epkinly sets ‘new standard of care’ in first-line lymphoma in Phase 3
Adding AbbVie and Genmab's Epkinly to R-CHOP cut the risk of disease progression or death by 51% in newly diagnosed diffuse large B cell lymphoma, hitting the primary endpoint of the 900-patient Phase 3 EPCORE DLBCL-2 trial. The benefit exceeded analyst expectations of 30-35%, was consistent across high-risk and low- to intermediate-risk disease, and beats the 27% and 25% reductions reported for Polivy and Monjuvi regimens, positioning Epkinly as a potential first-line standard of care.
Iberdomide Combination Halves Progression Risk in EXCALIBER-RRMM Relapsed Myeloma Trial
Median progression-free survival reached 42 months for iberdomide plus daratumumab and dexamethasone (IberDd), versus daratumumab plus bortezomib and dexamethasone, with a progression-free survival hazard ratio of 0.49. Bristol Myers Squibb reported the positive EXCALIBER-RRMM study results, which evaluated efficacy and safety in 800 multiple myeloma patients at first relapse or later.
Takeda's TAK-279 Beats Deucravacitinib Head-to-Head in Phase 3 Psoriasis Trials
Takeda's zesosutinib (TAK-279), an oral high-selectivity TYK2 inhibitor in development, showed statistical superiority over deucravacitinib on the primary endpoint and all key secondary endpoints in the Phase 3 LATITUDE Atlas head-to-head study in adults with moderate to severe plaque psoriasis. Complete skin clearance was seen in more patients as early as week 8, and by week 16 more than 2.5 times as many patients on zesosutinib achieved complete clearance as on deucravacitinib.
Regulators Green-Light Five New Options
On this pageThe FDA approved atezolizumab plus chemotherapy for adjuvant Stage III mismatch repair deficient colon cancer (ATOMIC, DFS HR 0.50), and tucatinib with trastuzumab and pertuzumab for HER2-positive breast cancer maintenance (median PFS 24.9 versus 16.3 months, HR 0.64). Novartis' remibrutinib gained approval for symptomatic dermographism, making it the only drug approved for both most common chronic urticaria types. Pritelivir was approved for acyclovir-resistant herpes lesions in immunocompromised adults, with 63% healing within 28 days versus 34%. China's NMPA approved Dato-DXd for metastatic triple-negative breast cancer, the first TROP2 ADC with an overall survival benefit there.
FDA approves atezolizumab in combination with chemotherapy for Stage III mismatch repair deficient colon cancer
The FDA approved atezolizumab (Tecentriq, Genentech) in combination with a fluoropyrimidine and oxaliplatin on October 8, 2026, for adjuvant treatment of Stage III mismatch repair deficient colon cancer in patients two years of age and older, with the subcutaneous Tecentriq Hybreza approved for those 12 years and older weighing 40 kg or greater. In the ATOMIC trial of 711 adults and one pediatric patient, the hazard ratio for disease-free survival was 0.50 versus mFOLFOX6 alone, and median DFS was not reached in either arm. Reviews are ongoing at partner agencies under Project Orbis.
FDA approves tucatinib with trastuzumab and pertuzumab for the maintenance treatment of HER2-positive breast cancer
The FDA approved tucatinib (Tukysa, Seagen, a Pfizer subsidiary) with trastuzumab and pertuzumab on October 7, 2026, for maintenance treatment of adults with unresectable locally advanced or metastatic HER2-positive breast cancer after induction therapy. In the 654-patient HER2CLIMB-05 trial, median progression-free survival was 24.9 months with tucatinib 300 mg twice daily versus 16.3 months with placebo (HR 0.64, p<0.0001). The label carries a boxed warning for hepatotoxicity; overall survival data were immature.
FDA Approves Novartis Remibrutinib for Symptomatic Dermographism in Adults
The FDA has approved Novartis' Rhapsido (remibrutinib) for adults with symptomatic dermographism whose symptoms are not adequately controlled by H1 antihistamines. The decision on October 7, 2026, follows the drug's September 2025 approval in chronic spontaneous urticaria, making Rhapsido the only prescription medicine approved for both of the most common chronic urticaria types.
FDA Approves Drug to Treat Lesions Caused by Herpes Simplex Virus
FDA has approved Hovilpri (pritelivir) tablets for immunocompromised adults with mucocutaneous herpes simplex virus lesions who did not respond to acyclovir, valacyclovir or famciclovir. In the Phase 3 PRIOH-1 Part C trial of 101 adults, all lesions healed within 28 days in 63% of pritelivir patients versus 34% on investigator-chosen treatments. The drug received priority review, and headache was the most common adverse reaction.
FDA Authorizes First Autonomous Robotic Blood Draw Device
China NMPA Approves Dato-DXd for Second Breast Cancer Indication in mTNBC
China's NMPA approved datopotamab deruxtecan (Dato-DXd) on September 29, 2026 for adults with unresectable or metastatic triple-negative breast cancer who are not suitable for PD-1/PD-L1 inhibitor treatment. It is the first and only TROP2-targeting ADC approved for this indication with an overall survival benefit, and it marks Dato-DXd's second breast cancer approval in China after HR-positive, HER2-negative advanced breast cancer.
Lineage Tracing, Ferroptosis and Microbiome Insights
On this pageTwo Science and Cell studies reconstructed mouse lineage at scale: DNA Typewriter built a 1.28-million-cell tree from zygote to E13.5, and PEtracer resolved about 75% of divisions across more than 1.4 million cells from 16 embryos; monoclonal gastruloid work showed fate biases arise before induction. Ferroptosis research revealed glutathione suppressing cell death via FSP1 independent of GPX4, and tumors outcompeting T cells for vitamin B2 via SLC52A2, with B2 supplementation boosting CAR-T efficacy. Janelia published the first complete adult male fly CNS connectome after nearly 20 years. Microbiome studies tied flagellated Lachnospiraceae to vaccine fever and identified a gut microbial odd-chain fatty acid that alleviates atherosclerosis in mice.
DNA Typewriter Reconstructs Mouse Cell Lineage Tree from Zygote to E13.5
A DNA Typewriter recorded cell lineage in a living mouse, and from a single embryo the team reconstructed a phylogenetic tree rooted at the zygote, time-calibrated to E13.5, containing 1.28 million cells annotated with transcriptomes. The work, by Chengxiang Qiu with Jay Shendure's group at the University of Washington, published in Science on October 9, 2026, closes a 50-year gap since Sulston manually traced a nematode's cell divisions. The tree reveals clonal dominance during gastrulation, hierarchical structure coupled to cell type, and ancestral state paths.
Comprehensive lineage tracing maps the landscape of cell fate decisions in mouse embryogenesis.
PEtracer, a method that continuously installs heritable genetic marks, reconstructed lineage trees resolving ~75% of cell divisions across >1.4 million cells from 16 replicate mouse embryos, paired with deep transcriptional profiling. The resulting quantitative reference shows reproducible lineage architecture between replicate embryos and maps fate biases, restriction timing, progenitor pool sizes and lineage relationships, including progressive neural crest restriction and distinct mesodermal origins of endothelium. It replaces piecemeal fate maps with a whole-embryo, cell-level lineage reference for mammalian development.
A fluctuation test for gastruloid heterogeneity.
Organoid heterogeneity traces partly to heritable differences in founder stem cells, not just culture conditions. Monoclonal gastruloids grown from single mouse embryonic stem cells showed extensive variability in development, mesodermal versus neural bias, and atypical cell types. DNA Typewriter lineage recording showed that fate biases arise before gastruloid induction, with more closely related founders producing more phenotypically similar gastruloids, and that fate-predictive differences map to gene expression, chromatin accessibility and imprinted loci.
A non-canonical function of glutathione to suppress ferroptosis via FSP1.
Glutathione suppresses ferroptosis independently of GPX4, protecting GPX4 knockout cells through a pathway pinpointed by genome-wide CRISPR-Cas9 screening: ferroptosis suppressor protein 1 (FSP1). FSP1 uses GSH to generate reduced ubiquinone, which scavenges oxidized lipids, and inhibition of FSP1 abolishes this protection in vitro and in vivo. The pathway differs from NAD(P)H-driven ubiquinone reduction by not requiring FAD.
Cancer competition for vitamin B2 creates metabolic checkpoint for T cell ferroptosis.
Tumors use the transporter SLC52A2 to scavenge vitamin B2 and outcompete T cells, which depend on SLC52A3-mediated B2 uptake. Deprived T cells lose mitochondrial respiration and glutathione regeneration, undergo mitophagy, labile iron accumulation, and lipid peroxidation, and die by ferroptosis. Deleting tumor SLC52A2 restores T cell function in immunocompetent hosts, and B2 supplementation or SLC52A3 overexpression boosts CAR-T antitumor efficacy. High tumoral SLC52A2 correlated with T cell dysfunction and poor survival.
Cell Publishes First Complete Connectome of the Adult Male Fruit Fly CNS
A team at the Howard Hughes Medical Institute's Janelia Research Campus has delivered the first complete connectome of the male fruit fly central nervous system, published in Cell. The project began in 2008 and took nearly 20 years, a pace the team achieved by iterating imaging and computational reconstruction methods. The work extends connectome mapping from the 302-neuron C. elegans wiring diagram, which itself took more than a decade, to a complex behaving brain.
The human gut microbiome primes fever after vaccination.
Gut microbiome composition before vaccination predicts fever risk after SARS-CoV-2 mRNA vaccines. In 171 healthy adults, fever risk correlated with low-grade intestinal inflammation, higher abundance of flagellated Lachnospiraceae bacteria, and increased flagellin expression. Fecal microbiomes from fever-high donors triggered stronger inflammation in human intestinal organoids and drove flagellin-dependent vaccine reactions in gnotobiotic mice, and both flagellin phenotypes and murine reactions were modifiable by diet. This positions the gut microbiome as a driver of vaccine-induced fever and a potential target for reducing side effects.
A gut microbial odd-chain fatty acid alleviates atherosclerosis in mice
The paper reports that a gut microbial odd-chain fatty acid alleviates atherosclerosis in mice. The work draws on mouse experiments together with human gut metagenomic datasets from atherosclerotic cardiovascular disease and subclinical carotid atherosclerosis cohorts, and includes RNA-seq data and molecular docking against the human HMGCR structure.
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